"Crizanlizumab in Sickle Cell Disease". The New England Journal of Medicine. 2016.

Clinical Question

Does crizanlizumab, an antibody against P-selectin, reduce the rate of sickle cell–related pain crises in patients with sickle cell disease?

Bottom Line

Crizanlizumab significantly decreased the frequency of sickle cell–related pain crises compared to placebo and showed a low rate of adverse effects in patients with sickle cell disease.

Major Points

Guidelines

As of the last update, there is no specific mention of crizanlizumab in current guidelines for the treatment of sickle cell disease.

Design

Multicenter, double-blind, randomized, placebo-controlled, phase 2 trial.
N=198 patients with sickle cell disease.
Intervention groups: low-dose crizanlizumab (2.5 mg/kg), high-dose crizanlizumab (5.0 mg/kg), vs. placebo.
52 weeks of intravenous treatment followed by a 6-week follow-up.
Primary outcome: Sickle cell–related pain crises rate.

Population

Inclusion Criteria: Patients 16-65 years old with sickle cell disease experiencing 2-10 pain crises in the previous 12 months.
Exclusion Criteria: Long-term red-cell transfusion therapy.

Interventions

High-dose crizanlizumab (5.0 mg/kg), low-dose crizanlizumab (2.5 mg/kg), or placebo given intravenously.

Outcomes

Primary Outcomes: Annual rate of pain crises was 1.63 with high-dose crizanlizumab vs. 2.98 with placebo (45.3% lower rate with high-dose, P=0.01).
Secondary Outcomes:
- Median time to first crisis: 4.07 months with high-dose vs. 1.38 months with placebo (P=0.001).
- Median time to second crisis: 10.32 months with high-dose vs. 5.09 months with placebo (P=0.02).
- A nonsignificant reduction in the median rate of days hospitalized (P=0.45).
- A 62.9% lower rate in annual uncomplicated crises (P=0.02).
- No significant effect on the acute chest syndrome.

Criticisms

- Long-term safety and immunogenicity require further monitoring.
- No significant changes were observed in markers of hemolysis.
- The impact on patients with genotypes other than HbSS needs further investigation.

Funding

Funded by Selexys Pharmaceuticals, NIH, and FDA. Authors disclosed financial relationships with Selexys and other pharmaceutical companies.

Further Reading